Ac-Tyr-Val-Ala-OH | 143382-04-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Ac-Tyr-Val-Ala-OH
• 英文别名: (S)-2-((S)-2-((S)-2-acetamido-3-(4-hydroxyphenyl)propanamido)-3-methylbutanamido)propanoic acid；N-acetyl-(L)-tyrosinyl-(L)-valinyl-(L)-alanine；acetyl-L-tyrosyl-L-valyl-L-alanine；(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]propanoic acid
• CAS: 143382-04-1
• 化学式: C₁₉H₂₇N₃O₆
• 分子量: 393.44
• InChiKey: WGYHAEUCHXNWLQ-UVBJJODRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  145
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-3-amino-4,4-dimethoxybutanoic acid 1,1-dimethylethyl ester 、 Ac-Tyr-Val-Ala-OH 在 N-甲基吗啉 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以35%的产率得到Ac-Tyr-Val-Ala-D-Asp(O^tBu)-H dimethyl acetal
  参考文献：
  名称：

  Synthesis and Evaluation of Enantiomeric Purity of Protectedα-Amino and Peptide Aldehydes

  摘要：

  The synthesis of enantiomerically pure Ac-Tyr-Val-Ala-Asp(O'Bu)-H dimethyl acetal ((S)-1) is reported, a protected tetrapeptide C-terminal aldehyde belonging to a class of potent, reversible inhibitors of cysteine proteases (e.g.. interleukin-1 beta-converting enzyme (ICE), also called caspase-1). The coupling of the precursors Ac-Tyr-Val-Ala-OH ((S)-8) and H-Asp(O'Bu)-H dimethyl acetal ((S)-6) gave (S)-1 in a yield of 85%, with epimerization of < 2% at the alanine and aspartic-acid residue. (S)-6 itself was synthesized in four steps in an overall yield of 83% with an ee >98%.

  DOI：

  10.1002/(sici)1522-2675(19991110)82:11<1960::aid-hlca1960>3.0.co;2-2
• 作为产物：
  描述：

  methyl acetyl-L-tyrosyl-L-valyl-L-alaninate 在 百里酚酞 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 以0.37 g (1.0 mmol. 63%)的产率得到Ac-Tyr-Val-Ala-OH
  参考文献：
  名称：

  (3R)-3-amino-4-carboxybutyraldehyde derivatives inhibiting the release of interleukin-1/beta

  摘要：

  该发明涉及一种新的通式(I)的(3R)-3-氨基-4-羧基丁醛衍生物，其中X代表C1-4烷氧羰基，可选择性取代的苯基-(C1-2烷氧)-羰基，C1-4烷基羰基或可选择性取代的苯基-(C1-3烷基)-羰基，n代表1或0，Y代表当n=1时的四肽通式Y4-Y3-Y2-Y1，三肽通式Y3-Y2-Y1或二肽通式Y2-Y1或氨基酸残基通式Y1，或者当n=0时，α-羟基酰三肽通式Q4-Y3-Y2-Y1，α-羟基酰二肽通式Q3-Y2-Y1或α-羟基酰-氨基酰残基通式Q2-Y1；其中Y1-Y4代表从以下L-或D-氨基酸组中选择的残基：丙氨酸、异亮氨酸、环己基甘氨酸、苯丙氨酸、谷氨酰胺、组氨酸、异亮氨酸、亮氨酸、赖氨酸、蛋氨酸、环戊胺基乙酸、脯氨酸、酪氨酸和缬氨酸；Q2-Q4代表从以下R或S构型的α-羟基酸中选择的酰基：2-环庚基-2-羟基乙酸、2-环己基-2-羟基乙酸、3-环己乳酸、3-苯乳酸、2-羟基-3-甲基丁酸、2-羟基-3-甲基戊酸、苹果酸或乳酸，以及与有机或无机碱形成的盐，以及含有这些化合物的药物组合物。该发明的通式(I)化合物是有价值的白细胞介素-1β转化酶的抑制剂。

  公开号：

  US06593300B1

文献信息

• Caspase inhibitors
  申请人：Thomas Craig

  公开号：US09365612B2

  公开（公告）日：2016-06-14

  A compound, or a pharmaceutically acceptable salt or ester thereof, of formula I: X—W wherein X is a caspase-selective structure and W has the structure of —NH—CH(Y)(Z) wherein Y is a structure that can form a reversible covalent bond with a caspase; and Z is selected from a carboxyl moiety or a carboxylic acid mimetic.

  公式I:X-W的化合物或药学上可接受的盐或酯，其中X是一种选择性卡他蛋白酶结构，W具有如下结构：—NH—CH(Y)(Z)，其中Y是一种能够与卡他蛋白酶形成可逆共价键的结构；Z选自羧基或羧酸类似物。
• Peptidyl derivatives as inhibitors of interleukin-1B converting enzyme
  申请人：MERCK & CO. INC.

  公开号：EP0547699A1

  公开（公告）日：1993-06-23

  Novel peptidyl derivatives of formula I are found to be potent inhibitors of interleukin-1β converting enzyme (ICE). Compounds of formula I may be useful in the treatment of inflammatory or immune-based diseases of the lung and airways; central nervous system and surrounding membranes; the eyes and ears; joints, bones, and connective tissues; cardiovascular system including the pericardium; the gastrointestinal and urogenital systems; the skin and mucosal membranes. Compounds of formula I are also useful in treating the complications of infection (e.g., gram negative shock) and tumors in which IL 1 functions as an autocrine growth factor or as a mediator of cachexia.

  公式I的新型肽衍生物被发现是强效的白细胞介素-1β转化酶（ICE）抑制剂。公式I的化合物可能在治疗肺和呼吸道的炎症或免疫性疾病；中枢神经系统和周围膜；眼睛和耳朵；关节、骨骼和结缔组织；包括心包在内的心血管系统；胃肠和泌尿生殖系统；皮肤和粘膜膜方面有用。公式I的化合物也有用于治疗感染的并发症（例如革兰氏阴性休克）和肿瘤，其中IL 1作为自分泌生长因子或消瘦介质。
• Inhibitors of interleukin-1 beta converting enzyme
  申请人：Bemis W. Guy

  公开号：US20080070953A1

  公开（公告）日：2008-03-20

  The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against interleukin-1 mediated diseases, including inflammatory diseases, autoimmune diseases and neurodegenerative diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

  本发明涉及一种新型的化合物类别，它们是白细胞介素-1β转化酶的抑制剂。本发明的ICE抑制剂具有特定的结构和物理化学特征。本发明还涉及包含这些化合物的制药组合物。本发明的化合物和制药组合物特别适用于抑制ICE活性，因此可以作为对白细胞介素-1介导的疾病，包括炎症性疾病、自身免疫性疾病和神经退行性疾病的治疗药物。本发明还涉及使用本发明的化合物和组合物抑制ICE活性的方法以及治疗白细胞介素-1介导的疾病的方法。
• Tripeptide &agr;-ketoamides
  申请人：Georgia Tech Research Corporation

  公开号：US06235929B1

  公开（公告）日：2001-05-22

  A novel class of tripeptide &agr;-ketoamides useful for selectively inhibiting serine proteases, selectively inhibiting cysteine proteases, generally inhibiting all serine proteases, and generally inhibiting all cysteine proteases, having the formula M1—AA—AA—AA—CO—NR3R4.

  一种新型三肽α-酮酰胺类化合物，适用于选择性抑制丝氨酸蛋白酶、选择性抑制半胱氨酸蛋白酶、普遍抑制所有丝氨酸蛋白酶和普遍抑制所有半胱氨酸蛋白酶，化学式为M1-AA-AA-AA-CO-NR3R4。
• Inhibitors of interleukin-1β converting enzyme
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US07772366B2

  公开（公告）日：2010-08-10

  The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against interleukin-1 mediated diseases, including inflammatory diseases, autoimmune diseases and neurodegenerative diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

  本发明涉及一种新型化合物类别，其为白细胞介素-1β转化酶的抑制剂。本发明的ICE抑制剂具有特定的结构和物理化学特征。本发明还涉及包含这些化合物的制药组合物。本发明的化合物和制药组合物特别适用于抑制ICE活性，因此，可作为对白细胞介素-1介导疾病，包括炎症性疾病、自身免疫性疾病和神经退行性疾病的治疗剂。本发明还涉及使用本发明的化合物和组合物抑制ICE活性的方法和治疗白细胞介素-1介导疾病的方法。